Langenbecks Arch Surg DOI 10.1007/s00423-014-1173-y
REVIEW ARTICLE
Approaches to assessing the benefits and harms of medical devices for application in surgery Stefan Sauerland & Anne Catharina Brockhaus & Naomi Fujita-Rohwerder & Stefano Saad
Received: 14 January 2014 / Accepted: 3 February 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background The surgical community and the medical device industry enjoy a fruitful cooperation for the benefit of patients, but during the last years several high-risk products have led to problems and scandals, thus highlighting the need for reforms in European CE marking requirements. In October 2013, the European Parliament voted on a draft regulation on medical devices that intends to replace the current directives in 2014. Purpose This article offers guidance to surgeons on how to select and assess medical devices for clinical use. Examples include artificial sphincters, surgical meshes, as well as singleincision and robot-assisted surgery. It is important that surgeons have a basic understanding of the requirements for CE marking of new medical devices. Because device performance rather than effectiveness is required for European market entry, surgeons (and their patients) are often left with the burden of using potentially harmful devices. In addition, potential problems concerning the safety or effectiveness of approved devices are concealed by the lack of data transparency. Because regulatory reforms were blocked at the European level, many member states will now seek other ways of restricting the use of
medical devices with unknown effectiveness. One interesting model in this regard is to link the reimbursement of new medical devices to the conduct of clinical trials. Conclusions Surgeons should develop a structured multidisciplinary approach to innovation management in their hospitals before using a new high-risk device. The key question is how to strike the right balance between innovation and safety. Keywords Medical devices . Device approval . Europe . Clinical trials . Diffusion of innovation
S. Sauerland Institute for Research in Operative Medicine (IFOM), University of Witten/Herdecke, Cologne, Germany
Medical devices are indispensable in health care, especially in surgery, where many operations are technically feasible only because innovative instruments, implants or imaging tools have been developed. Medical devices also represent an important economic factor for many countries, and Germany is currently the largest exporter of medical devices in Europe. This leading role of the German healthcare industry can be attributed to the past and present inventiveness of the country’s clinicians and researchers. The liberal regulatory framework, however, which helped the medical device industry to prosper, has also led to a series of severe problems and scandals in recent years. This article presents an overview of the latest developments in medical device regulation and provides recommendations on how surgeons can make best use of medical devices, while avoiding problems associated with possible harms or liability. We will address the key questions that should be asked by surgeons in the context of medical devices.
A. C. Brockhaus Institute for Health Economics and Clinical Epidemiology, University of Cologne, Cologne, Germany
Deciding on the use of a new medical device
S. Saad Department of General Surgery, Clinic Gummersbach, Academic Hospital University of Cologne, Cologne, Germany
It can be estimated that every year about 150 new high-risk medical devices are introduced to the European market.
S. Sauerland (*) : A. C. Brockhaus : N. Fujita-Rohwerder Institute for Quality and Efficiency in Health Care (IQWiG), Im Mediapark 8, 50670 Cologne, Germany e-mail: [email protected]
Langenbecks Arch Surg
However, as many of these devices are either not relevant for surgery or represent only minor modifications of existing products, surgeons are probably confronted with only about five to ten new medical devices per year. Usually, these devices will already have a CE mark (‘Conformité Européenne’), which allows the company to sell their product in the European Economic Area. Before high-risk devices can be CE marked, they have to be assessed by a ‘notified body’, a technical review company hired by the manufacturers to certify the quality of the device. The requirements for CE marking (and thus market access) vary according to the risk class and are highest for class IIb devices (including most surgical implants) and class III devices (such as cardiovascular implants and large joint prostheses). The process of CE marking has come under increased scrutiny lately, after a French company (Poly Implant Prothèse, PIP) repeatedly deceived their German notified body (TÜV Rheinland) and sold about 300,000 low-quality breast implants filled with industrial silicone. In 2012, the European Commission reacted to this scandal and proposed rules to raise the necessary standards for a notified body’s competence and increase the level of auditing in medical device companies (e.g. through unannounced on-site visits). Although these measures are certainly useful to prevent future quality problems with medical devices, the European Commission failed to address the most basic problem in device regulation, i.e. the fact that new medical devices are only required to have proven safety and performance, but without any requirement to show clinical benefits in terms of efficacy or effectiveness. Even the very basic idea that the clinical evaluation of a new medical device should aim at measuring clinical benefits was not easy to establish at a European level. Furthermore, there is still no regulation to require manufacturers to perform randomized controlled trials (RCTs) for new devices. On 22 October 2013, European politicians compromised common scientific principles and agreed on a new provision that still leaves the backdoor open: ‘As randomised controlled investigations usually generate a higher level of evidence for clinical efficacy and safety, the use of any other design or study has to be justified. Also the choice of the control intervention shall be justified’ [1]. Accordingly, many devices are CE marked on the basis of little more than case series of about 50 cases. One of the more recent surgical examples is the magnetic esophageal sphincter, which entered the European market in early 2010. Clinical data, as required by law, primarily consisted of a feasibility study conducted in 44 patients with gastro-esophageal reflux disease. However, a study comparing magnetic sphincter implantation versus fundoplication (the current standard of care) is lacking. Table 1 provides a selective overview of this and several other more recent medical devices that have already had an impact or could have a future impact on
general surgery. For most of these ‘innovations’, high-quality evidence is either lacking or shows no relevant improvement over current standards of surgery. Clinicians should therefore always keep in mind that new CE-marked medical devices are potentially ineffective. Especially for high-risk devices, this implies that the riskbenefit ratio is uncertain and may invert to more harm than benefit if future studies fail to show the anticipated benefits [2–4]. Recently, orthopedic surgeons had to learn this bitter lesson when metal-on-metal hip implants were found to fail in an alarmingly high proportion of patients [5]. Several other examples show that among the large number of medical devices with unknown effectiveness, some will turn out to be ineffective or even harmful. It can only become evident whether this is the case after higher-level clinical studies have been performed [4, 6, 7]. Such studies are often performed only when a device company plans to enter the US market. As the Food and Drug Administration (FDA) usually— but not always—requests better clinical evidence than European notified bodies, new high-risk devices are usually available about 2 years earlier on the market in Europe as compared to the United States [8–11]. During this time span (and even longer, if the device is not marketed in the United States), surgeons in Europe have to gamble with the risk of using or implanting ineffective or harmful devices [12]. Surgeons are used to making decisions under uncertainty and time pressure, but it can be extremely difficult to choose between innovation and patient safety. However, a tendency often prevails to be innovative and to suppress one’s doubts, even if the clinical need for a new device is limited [13, 14]. Surgeons may sometimes even face pressure from patients and the media to introduce innovations with perceived added value. In an area where competition between hospitals is intense, one might choose to use an innovation just because the local media will hail this event as a sign of a hospital’s quality. However, a more rational and structured assessment is necessary, and this should include a thorough review of the new device’s advantages and disadvantages, with all issues clearly separated into those with and those without supporting clinical evidence [15]. Ideally, surgeons are assisted by a multidisciplinary team (or a standing hospital committee) with expertise in evaluating medical procedures in an evidence-based way [16–18]. If surgical journals provided a regular section on new medical devices, readers might be more interested in evidence-based and independent reviews. Clinical, economic and strategic arguments have to be weighed against one another. If a decision is made in a hospital to use a new device or procedure for which clinical data are sparse, there should always be some form of concurrent quality control, ideally within more formal research as described below, followed by a re-evaluation.
Langenbecks Arch Surg Table 1 Important new medical devices with an impact on general surgery
a
Evidence levels: 1 = randomized controlled trials (RCTs) or systematic review of RCTs; 2 = higher-quality (e.g. prospective) controlled studies; 3 = lower quality (e.g. retrospective) controlled studies; 4 = cohort studies without a control group (i.e. case series); 5 = non-clinical data or expert opinion
Highest level of evidencea
Key clinical studies or reviews
Current best conclusion on effectiveness
Titanium clips for appendectomy Single-incision multi-port trocars for appendectomy for cholecystectomy for colorectal resection Negative pressure wound therapy for chronic or acute skin wounds for anastomotic leakage Magnetic sphincter augmentation for gastro-esophageal reflux disease
1
[36]
unclear
1 1 2
[37] [38, 39] [40]
no relevant difference no relevant difference unclear
1 2
[41, 42] [43]
unclear unclear
4
[44, 45]
unclear
for fecal incontinence Electrical lower esophageal sphincter stimulation Sacral nerve stimulation for fecal incontinence Duodenal-jejunal bypass sleeve Biologic meshes for incisional hernia Ultrasonic dissection devices Robotic assistance for fundoplication for bariatric surgery for gastrectomy
3 4
[46, 47] [48]
unclear unclear
1
[49]
unclear
1 4 1
[50] [51] [52]
unclear unclear minor advantages
1 1 3
[53] [54] [55]
no relevant difference unclear unclear
Selecting between existing devices Once a new device has entered the market, several very similar products will commonly follow. This leaves the surgeon with the choice of either buying the original leading product or a similar follow-up product. This decision should again be based on a thorough assessment of product safety, clinical effectiveness and costs. All too often, traditional costcontainment efforts directed at device purchase prices will prefer cheaper products, even though data on safety and effectiveness are mostly absent. Follow-up products can usually be offered at a lower price, because the manufacturers of such devices save on innovation costs and are not obliged to submit the same amount of data as was necessary for the first product. The first innovative product often has to prove safety and technical performance on the basis of clinical data, whereas follow-up products can be CE marked on the basis of their technical equivalence to the first product. Non-clinical data alone (combined with clinical data from the literature) may therefore be sufficient for the market access of a ‘me-too product’, which allows the manufacturer to offer his product at a much lower price. Furthermore, follow-up products are often only inadequately blocked by current patent law. Principally, European patents are valid for 20 years, but it is often possible to construct similar devices without infringing patent law. Furthermore, scientific theories and medical
procedures are unpatentable. ‘Me-too products’ are therefore an early and frequent problem, especially when the new device is less complex, such as an interspinous spacer. As a result, investment in clinical trials sometimes does not pay off for innovative device manufacturers. This difference in the patenting of drugs and devices allows the prices of many new devices to fall quickly after market entry but on the other hand impedes the conduct of clinical research. In effect, clinical data—and especially head-to-head comparisons—are frequently lacking. When trying to find data on a single device or a group of medical devices, surgeons will often have difficulties in finding information, because preclinical and clinical data on medical devices may exist but are kept on file by the manufacturer. Transparency—or more precisely, the lack of it—has been identified as a major problem in the evaluation of medical devices [11, 19]. Currently, there is no obligation for manufacturers or notifying bodies to publish clinical results data from CE dossiers. Any such publication might even help competitor manufacturers and is thus avoided. In addition, the European Databank of Medical Devices (EUDAMED), which could give surgeons an overview of all recently approved medical devices, together with the supporting clinical and non-clinical data, is not publicly accessible. Thus, it is impossible for clinicians and patients to make informed choices between different medical devices licensed for the
Langenbecks Arch Surg
same indication. When making decisions, surgeons can rely only on marketing materials and a few published clinical studies. This explains why even scientific surgeons make use of clinical experience, theoretical insights and personal communication. In the end, the lack of data transparency leads to an often unstructured, heterogeneous and erroneous innovation management in surgical departments all over Europe. There is some hope for an increase in transparency of clinical data on medical devices through the revised European regulation. On 22 October 2013, the European Parliament agreed that a ‘summary of the safety and performance report should be publicly available via EUDAMED’ [1], but this new transparency applies only to high-risk medical devices. In this regard, lessons can be learned from the regulatory procedures in the United States, where all relevant data are publicly accessible. On the FDA website, it is easy, for example, to find out which adjustable gastric banding systems have been approved and which clinical data were submitted for approval. European surgeons should make better use of this information source, also because of the higher standards of regulatory approval in the United States. It is worthwhile remembering that PIP silicone implants, robot surgery for total hip arthroplasty and many other harmful devices were never licensed for use in the United States [12]. There are even examples of US companies that first introduced their devices to the European market due to the lower regulatory hurdles. In this regard, European patients are being used as guinea pigs, often without being properly informed about the risks and benefits of new devices [20].
Evaluating devices in the hospital setting ‘No innovation without evaluation.’ This was one of the key statements of the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) surgical experts group [21–24]. It has also been recommended to perform prospective studies in the early phase of surgical innovation, where patient selection criteria and learning curve effects still have to be optimized [25]. In the second or main phase of evaluation, RCTs should be conducted. The pitfall to be avoided is acceptance of preliminary non-randomized data as proof of the new devices or procedure’s superiority [26]. It is beyond question that the RCT is the study design of choice for an unbiased assessment of treatments, and this pertains also to medical devices and surgical procedures [27, 28]. Thus, it is best to initiate an RCT when changing treatment in any relevant way. In surgery, however, it may be first necessary to overcome the learning curve. This may be worthwhile for proper planning of the RCT, for which useful patient selection criteria, suitable outcome measures and realistic effect size estimates are crucial.
Nevertheless, even in the context of a prospective study without a control group, full reporting of all results is necessary to ensure the validity of data on procedure feasibility. Besides scientific reporting of complete intention-to-treat results on a consecutive series of patients, it is also important to be compliant with reporting requirements for medical devices. Although safe innovation requires full reporting of potential problems, many surgeons do not file reports of complications to their national authority or the device manufacturer [29–31]. The apparent but deceptive absence of critical or negative reports strongly contributes to the enthusiasm that surrounds many new medical devices in their early phase. Figure 1 shows the course that some new devices and procedures take, once the initial enthusiasm wanes. The European Parliament has lately emphasized the importance of reporting complications that have occurred with the use of medical devices. In the future, manufacturers have to provide periodic safety update reports (PSURs) for all class III medical devices. Until today, PSURs were required only for drugs (i.e. pharmacovigilance). This regulatory step therefore shows that devices can be effectively assessed by similar methods as drugs. However, such reporting is not yet deemed necessary for class IIb products, which represent the majority of surgical implants. Furthermore, the PSURs will largely remain unpublished. Registries have recently drawn a lot of attention to the provision of ‘real-world’ data on medical devices. When data collection is carried out in a complete and valid way, registry studies may in fact offer valuable insights about the safety, application and quality of innovative health care. Device manufacturers are therefore sometimes requested to perform observational clinical studies for the Post-Market Surveillance (PMS) of new devices. Surgeons also try to set up registries to study new procedures or new devices, such as biologic mesh implants for hernia repair [32] or natural orifice transluminal endoscopic surgery [33]. Nevertheless, registry studies and
Fig. 1 The seven stages in the career of a medical innovation as described in the key article by John B. McKinlay [26]
Langenbecks Arch Surg
other observational studies do not generally allow reliable conclusions on effectiveness. It is often left to the scientific tenacity or enthusiasm of surgeons to fill these evidence gaps. The funding of clinical research, however, remains a constant challenge, and many highly relevant study ideas end up in low-quality research simply because most surgeons lack the resources to conduct their trials in multiprofessional collaboration.
Obtaining reimbursement for new devices As described above, many medical devices enter the European market without sufficient evidence of effectiveness. As the new European regulation will not essentially affect this highly problematic issue, it can be expected that different stakeholders will deal with this problem at a national level in each European country. It is easily understandable why national health insurance systems or statutory sickness funds deny payments for expensive medical devices with uncertain medical benefits. Highly innovative surgical departments will therefore experience problems with the reimbursement of new medical devices unless the manufacturer offers them a rebate. However, these reimbursement issues are highly dependent on the country a surgeon works in. They are thus considered to be beyond the scope of this article. A common trend in European health care is to link the reimbursement of new devices or procedures to participation in clinical research. This idea is often labelled as ‘coverage with evidence development’ (CED). Such a policy limits the application of new interventions to only a subset of wellselected patients treated within clinical trials in experienced centres. In addition, CED includes a reassessment of the intervention under question once the clinical trial has been completed. CED policies were initially installed in the United States and Canada, where they have proved to be useful [34, 35]. In late 2013, the new German government agreed on plans requiring that hospitals have to participate in clinical trials when using new high-risk medical devices in their patients. Hospitals that want to offer new surgical procedures will therefore have to train their staff in research methods, which in turn will also help to make better decisions on the use of existing devices. However, the key issue that will remain is: Who pays the costs of clinical research? It may also be difficult to draw a clear borderline between a new procedure and a new medical device.
Concluding remarks The vast majority of medical devices are safe and effective. This article is not intended to worry patients or surgeons, but the increasing complexity and invasiveness of medical
devices require a more critical attitude towards new products than previously shown. Scientific assessment of new medical devices should be as rigorous and regulated as for any other potentially harmful (or expensive) medical innovation. Surgeons should be reluctant to apply or implant new high-risk devices before high-quality evidence is published. In this context, it is a fundamental element of medical practice to appropriately inform the patient. As it is unlikely that the European regulation on device approval will become stricter, the reimbursement of medical devices will come increasingly into focus. Device manufacturers will become accustomed to the idea that RCTs are indispensable in determining clinical risks and benefits. The reimbursement of new high-risk devices will be formally linked to positive RCT results. Scientific surgeons who participate and collaborate in the different research activities will gain influence, as they will be the first to use and evaluate new devices for the benefit of patients.
Acknowledgments The authors thank Natalie McGauran for editorial support. Conflicts of interest None
References 1. European Parliament (2013) Amendments adopted by the European Parliament on 22 October 2013 on the proposal for a regulation of the European Parliament and of the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009. http://www.europarl.europa.eu/ sides/getDoc.do?type=TA&language=EN&reference=P7-TA-2013428 02 Accessed.January.2014 2. Hulstaert F, Neyt M, Vinck I, Stordeur S, Huic M, Sauerland S, Kuijpers MR, Abrishami P, Vondeling H, Van Brabandt H (2011) The pre-market clinical evaluation of innovative high-risk medical devices (KCE report 158C). Belgian Health Care Knowledge Centre, Brussels (Belgium) 3. Herrmann-Frank A, Lelgemann M (2013) Neue Medizinprodukte: Unzureichende Datenlage [New medical devices: insufficient evidence]. Dt Ärztebl 110(10):A432–A434 4. German National Associations of Statutory Health Insurance Funds (2013) Medical devices: the myths and the truth. http://www.aok-bv. de/imperia/md/aokbv/politik/versicherte/thesenpapier_gross_0913_ engl_1.pdf.02 Accessed January 2014 5. Cohen D (2011) Out of joint: the story of the ASR. BMJ 342:d2905 6. Cohen D (2012) EU approval system leaves door open for dangerous devices. BMJ 345:e7173 7. Storz-Pfennig P, Schmedders M, Dettloff M (2013) Trials are needed before new devices are used in routine practice in Europe. BMJ 346: f1646 8. Kramer DB, Xu S, Kesselheim AS (2012) Regulation of medical devices in the United States and European Union. N Engl J Med 366(9):848–855 9. Curfman GD, Redberg RF (2011) Medical devices—balancing regulation and innovation. N Engl J Med 365(11):975–977
Langenbecks Arch Surg 10. Kramer DB, Xu S, Kesselheim AS (2012) How does medical device regulation perform in the United States and the European Union? A systematic review. PLoS Med 9(7):e1001276 11. Krüger LJ, Wild C (2013) Evidence requirements for the authorization and reimbursement of high-risk medical devices in the USA, Europe, Australia and Canada (HTA Project Report No. 73). Ludwig Boltzmann Institute Health Technology Assessment, Vienna 12. Food and Drug Administration (FDA) (2012) Unsafe and ineffective devices approved in the EU that were not approved in the US. http:// www.elsevierbi.com/∼/media/Supporting%20Documents/The% 20Gray%20Sheet/38/20/FDA_EU_Devices_Report.pdf 02 Accessed January 2014 13. Anand R, Graves SE, de Steiger RN, Davidson DC, Ryan P, Miller LN, Cashman K (2011) What is the benefit of introducing new hip and knee prostheses? J Bone Joint Surg Am 93(Suppl 3):51–54 14. Lieberman JR, Wenger N (2004) New technology and the orthopaedic surgeon: are you protecting your patients? Clin Orthop Relat Res 429:338–341 15. Neugebauer EA, Becker M, Buess GF, Cuschieri A, Dauben HP, Fingerhut A, Fuchs KH, Habermalz B, Lantsberg L, Morino M, Reiter-Theil S, Soskuty G, Wayand W, Welsch T (2010) EAES recommendations on methodology of innovation management in endoscopic surgery. Surg Endosc 24(7):1594–1615 16. Selbmann HK (1997) Qualitäts—und Innovationsmanagement in der Chirurgie im Dienste des Patienten [Quality and innovation management in surgery for the patient’s benefit]. Langenbecks Arch Chir Suppl Kongressbd 114:872–879 17. Wright JG, Weinstein S (2013) The innovation cycle: a framework for taking surgical innovation into clinical practice. J Bone Joint Surg Am 95(21):e1641–e1645 18. Poulin P, Austen L, Kortbeek JB, Lafreniere R (2012) New technologies and surgical innovation: five years of a local health technology assessment program in a surgical department. Surg Innov 19(2):187–199 19. Hulstaert F, Neyt M, Vinck I, Stordeur S, Huic M, Sauerland S, Kuijpers MR, Abrishami P, Vondeling H, Flamion B, Garattini S, Pavlovic M, van Brabandt H (2012) Pre-market clinical evaluations of innovative high-risk medical devices in Europe. Int J Technol Assess Health Care 28(3):278–284 20. Falagas ME, Korbila IP, Giannopoulou KP, Kondilis BK, Peppas G (2009) Informed consent: how much and what do patients understand? Am J Surg 198(3):420–435 21. McCulloch P, Cook JA, Altman DG, Heneghan C, Diener MK (2013) IDEAL framework for surgical innovation 1: the idea and development stages. BMJ 346:f3012 22. Ergina PL, Barkun JS, McCulloch P, Cook JA, Altman DG (2013) IDEAL framework for surgical innovation 2: observational studies in the exploration and assessment stages. BMJ 346:f3011 23. Cook JA, McCulloch P, Blazeby JM, Beard DJ, Marinac-Dabic D, Sedrakyan A (2013) IDEAL framework for surgical innovation 3: randomised controlled trials in the assessment stage and evaluations in the long term study stage. BMJ 346:f2820 24. McCulloch P, Altman DG, Campbell WB, Flum DR, Glasziou P, Marshall JC, Nicholl J, Aronson JK, Barkun JS, Blazeby JM, Boutron IC, Clavien PA, Cook JA, Ergina PL, Feldman LS, Maddern GJ, Reeves BC, Seiler CM, Strasberg SM, Meakins JL, Ashby D, Black N, Bunker J, Burton M, Campbell M, Chalkidou K, Chalmers I, de Leval M, Deeks J, Grant A, Gray M, Greenhalgh R, Jenicek M, Kehoe S, Lilford R, Littlejohns P, Loke Y, Madhock R, McPherson K, Meakins J, Rothwell P, Summerskill B, Taggart D, Tekkis P, Thompson M, Treasure T, Trohler U, Vandenbroucke J (2009) No surgical innovation without evaluation: the IDEAL recommendations. Lancet 374(9695):1105–1112 25. Ramsay CR, Grant AM, Wallace SA, Garthwaite PH, Monk AF, Russell IT (2000) Assessment of the learning curve in health technologies. A systematic review. Int J Technol Assess Health Care 16(4):1095–1108
26. McKinlay JB (1981) From “promising report” to “standard procedure”: seven stages in the career of a medical innovation. Milbank Mem Fund 59:374–411 27. Walters BC, Sackett DL (1991) Why clinical research? In: Troidl H, Spitzer WO, McPeek B et al (eds) Principle and practice of research: strategies for surgical investigators, 2nd edn. Springer, New York, pp 231–248 28. Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (2011) Allgemeine Methoden: Version 4.0. https://www.iqwig.de/download/ IQWiG_Methoden_Version_4_0.pdf.02 Accessed January 2014 29. Samore MH, Evans RS, Lassen A, Gould P, Lloyd J, Gardner RM, Abouzelof R, Taylor C, Woodbury DA, Willy M, Bright RA (2004) Surveillance of medical device-related hazards and adverse events in hospitalized patients. JAMA 291(3):325–334 30. Cooper MA, Ibrahim A, Lyu H, Makary MA (2013) Underreporting of robotic surgery complications. J Healthc Qual 31. Fuller J, Ashar BS, Carey-Corrado J (2005) Trocar-associated injuries and fatalities: an analysis of 1399 reports to the FDA. J Minim Invasive Gynecol 12(4):302–307 32. Ansaloni L, Catena F, Coccolini F, Negro P, Campanelli G, Miserez M (2009) New “biological” meshes: the need for a register. The EHS registry for biological prostheses: call for participating European surgeons. Hernia 13(1):103–108 33. Arezzo A, Zornig C, Mofid H, Fuchs KH, Breithaupt W, Noguera J, Kaehler G, Magdeburg R, Perretta S, Dallemagne B, Marescaux J, Copaescu C, Graur F, Szasz A, Forgione A, Pugliese R, Buess G, Bhattacharjee HK, Navarra G, Godina M, Shishin K, Morino M (2013) The EURO-NOTES clinical registry for natural orifice transluminal endoscopic surgery: a 2-year activity report. Surg Endosc 27(9):3073–3084 34. Tunis SR, Pearson SD (2006) Coverage options for promising technologies: Medicare’s ‘coverage with evidence development’. Health Aff (Millwood) 25(5):1218–1230 35. Daniel GW, Rubens EK, McClellan M (2013) Coverage with evidence development for medicare beneficiaries: challenges and next steps. JAMA Intern Med 173(14):1281–1282 36. Ates M, Dirican A, Ince V, Ara C, Isik B, Yilmaz S (2012) Comparison of intracorporeal knot-tying suture (polyglactin) and titanium endoclips in laparoscopic appendiceal stump closure: a prospective randomized study. Surg Laparosc Endosc Percutan Tech 22(3):226–231 37. Markar SR, Karthikesalingam A, Di Franco F, Harris AM (2013) Systematic review and meta-analysis of single-incision versus conventional multiport appendicectomy. Br J Surg 100(13):1709–1718 38. Geng L, Sun C, Bai J (2013) Single incision versus conventional laparoscopic cholecystectomy outcomes: a meta-analysis of randomized controlled trials. PLoS One 8(10):e76530 39. Saad S, Strassel V, Sauerland S (2013) Randomized clinical trial of single-port, minilaparoscopic and conventional laparoscopic cholecystectomy. Br J Surg 100(3):339–349 40. Maggiori L, Gaujoux S, Tribillon E, Bretagnol F, Panis Y (2012) Single-incision laparoscopy for colorectal resection: a systematic review and meta-analysis of more than a thousand procedures. Colorectal Dis 14(10):e643–e654 41. Gregor S, Maegele M, Sauerland S, Krahn J, Peinemann F, Lange S (2008) Negative pressure wound therapy: a vacuum of evidence? Arch Surg 143(2):189–196 42. Webster J, Scuffham P, Sherriff KL, Stankiewicz M, Chaboyer WP (2012) Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention. Cochrane Database Syst Rev 4: Cd009261 43. Mees ST, Palmes D, Mennigen R, Senninger N, Haier J, Bruewer M (2008) Endo-vacuum assisted closure treatment for rectal anastomotic insufficiency. Dis Colon Rectum 51(4):404–410 44. Bonavina L, Saino G, Bona D, Sironi A, Lazzari V (2013) One hundred consecutive patients treated with magnetic sphincter
Langenbecks Arch Surg
45.
46.
47.
48.
49.
augmentation for gastroesophageal reflux disease: 6 years of clinical experience from a single center. J Am Coll Surg 217(4):577–585 Ganz RA, Peters JH, Horgan S, Bemelman WA, Dunst CM, Edmundowicz SA, Lipham JC, Luketich JD, Melvin WS, Oelschlager BK, Schlack-Haerer SC, Smith CD, Smith CC, Dunn D, Taiganides PA (2013) Esophageal sphincter device for gastroesophageal reflux disease. N Engl J Med 368(8):719–727 Wong MT, Meurette G, Stangherlin P, Lehur PA (2011) The magnetic anal sphincter versus the artificial bowel sphincter: a comparison of 2 treatments for fecal incontinence. Dis Colon Rectum 54(7):773–779 Wong MT, Meurette G, Wyart V, Lehur PA (2012) Does the magnetic anal sphincter device compare favourably with sacral nerve stimulation in the management of faecal incontinence? Colorectal Dis 14(6): e323–e329 Rodriguez L, Rodriguez P, Gomez B, Ayala JC, Saba J, PerezCastilla A, Galvao Neto M, Crowell MD (2013) Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial. Surg Endosc 27(4):1083–1092 Thin NN, Horrocks EJ, Hotouras A, Palit S, Thaha MA, Chan CL, Matzel KE, Knowles CH (2013) Systematic review of the clinical effectiveness of neuromodulation in the treatment of faecal incontinence. Br J Surg 100(11):1430–1447
50. Zechmeister-Koss I, Huic M, Fischer S (2013) Duodenal-jejunal bypass sleeve for the treatment of obesity with or without type II diabetes mellitus (EUnetHTA final report). http://www.eunethta.eu/ sites/5026.fedimbo.belgium.be/files/Endobarrier_Assessment.pdf.02 Accessed January 2014 51. Slater NJ, van der Kolk M, Hendriks T, van Goor H, Bleichrodt RP (2013) Biologic grafts for ventral hernia repair: a systematic review. Am J Surg 205(2):220–230 52. Contin P, Goossen K, Grummich K, Jensen K, Schmitz-Winnenthal H, Büchler MW, Diener MK (2013) ENERgized vessel sealing systems versus CONventional hemostasis techniques in thyroid surgery—the ENERCON systematic review and network meta-analysis. Langenbecks Arch Surg 398(8):1039–1056 53. Wang Z, Zheng Q, Jin Z (2012) Meta-analysis of robot-assisted versus conventional laparoscopic Nissen fundoplication for gastrooesophageal reflux disease. ANZ J Surg 82(3):112–117 54. Cirocchi R, Boselli C, Santoro A, Guarino S, Covarelli P, Renzi C, Listorti C, Trastulli S, Desiderio J, Coratti A, Noya G, Redler A, Parisi A (2013) Current status of robotic bariatric surgery: a systematic review. BMC Surg 13(1):53 55. Marano A, Choi YY, Hyung WJ, Kim YM, Kim J, Noh SH (2013) Robotic versus laparoscopic versus open gastrectomy: a metaanalysis. J Gastric Cancer 13(3):136–148
REVIEW ARTICLE
Approaches to assessing the benefits and harms of medical devices for application in surgery Stefan Sauerland & Anne Catharina Brockhaus & Naomi Fujita-Rohwerder & Stefano Saad
Received: 14 January 2014 / Accepted: 3 February 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background The surgical community and the medical device industry enjoy a fruitful cooperation for the benefit of patients, but during the last years several high-risk products have led to problems and scandals, thus highlighting the need for reforms in European CE marking requirements. In October 2013, the European Parliament voted on a draft regulation on medical devices that intends to replace the current directives in 2014. Purpose This article offers guidance to surgeons on how to select and assess medical devices for clinical use. Examples include artificial sphincters, surgical meshes, as well as singleincision and robot-assisted surgery. It is important that surgeons have a basic understanding of the requirements for CE marking of new medical devices. Because device performance rather than effectiveness is required for European market entry, surgeons (and their patients) are often left with the burden of using potentially harmful devices. In addition, potential problems concerning the safety or effectiveness of approved devices are concealed by the lack of data transparency. Because regulatory reforms were blocked at the European level, many member states will now seek other ways of restricting the use of
medical devices with unknown effectiveness. One interesting model in this regard is to link the reimbursement of new medical devices to the conduct of clinical trials. Conclusions Surgeons should develop a structured multidisciplinary approach to innovation management in their hospitals before using a new high-risk device. The key question is how to strike the right balance between innovation and safety. Keywords Medical devices . Device approval . Europe . Clinical trials . Diffusion of innovation
S. Sauerland Institute for Research in Operative Medicine (IFOM), University of Witten/Herdecke, Cologne, Germany
Medical devices are indispensable in health care, especially in surgery, where many operations are technically feasible only because innovative instruments, implants or imaging tools have been developed. Medical devices also represent an important economic factor for many countries, and Germany is currently the largest exporter of medical devices in Europe. This leading role of the German healthcare industry can be attributed to the past and present inventiveness of the country’s clinicians and researchers. The liberal regulatory framework, however, which helped the medical device industry to prosper, has also led to a series of severe problems and scandals in recent years. This article presents an overview of the latest developments in medical device regulation and provides recommendations on how surgeons can make best use of medical devices, while avoiding problems associated with possible harms or liability. We will address the key questions that should be asked by surgeons in the context of medical devices.
A. C. Brockhaus Institute for Health Economics and Clinical Epidemiology, University of Cologne, Cologne, Germany
Deciding on the use of a new medical device
S. Saad Department of General Surgery, Clinic Gummersbach, Academic Hospital University of Cologne, Cologne, Germany
It can be estimated that every year about 150 new high-risk medical devices are introduced to the European market.
S. Sauerland (*) : A. C. Brockhaus : N. Fujita-Rohwerder Institute for Quality and Efficiency in Health Care (IQWiG), Im Mediapark 8, 50670 Cologne, Germany e-mail: [email protected]
Langenbecks Arch Surg
However, as many of these devices are either not relevant for surgery or represent only minor modifications of existing products, surgeons are probably confronted with only about five to ten new medical devices per year. Usually, these devices will already have a CE mark (‘Conformité Européenne’), which allows the company to sell their product in the European Economic Area. Before high-risk devices can be CE marked, they have to be assessed by a ‘notified body’, a technical review company hired by the manufacturers to certify the quality of the device. The requirements for CE marking (and thus market access) vary according to the risk class and are highest for class IIb devices (including most surgical implants) and class III devices (such as cardiovascular implants and large joint prostheses). The process of CE marking has come under increased scrutiny lately, after a French company (Poly Implant Prothèse, PIP) repeatedly deceived their German notified body (TÜV Rheinland) and sold about 300,000 low-quality breast implants filled with industrial silicone. In 2012, the European Commission reacted to this scandal and proposed rules to raise the necessary standards for a notified body’s competence and increase the level of auditing in medical device companies (e.g. through unannounced on-site visits). Although these measures are certainly useful to prevent future quality problems with medical devices, the European Commission failed to address the most basic problem in device regulation, i.e. the fact that new medical devices are only required to have proven safety and performance, but without any requirement to show clinical benefits in terms of efficacy or effectiveness. Even the very basic idea that the clinical evaluation of a new medical device should aim at measuring clinical benefits was not easy to establish at a European level. Furthermore, there is still no regulation to require manufacturers to perform randomized controlled trials (RCTs) for new devices. On 22 October 2013, European politicians compromised common scientific principles and agreed on a new provision that still leaves the backdoor open: ‘As randomised controlled investigations usually generate a higher level of evidence for clinical efficacy and safety, the use of any other design or study has to be justified. Also the choice of the control intervention shall be justified’ [1]. Accordingly, many devices are CE marked on the basis of little more than case series of about 50 cases. One of the more recent surgical examples is the magnetic esophageal sphincter, which entered the European market in early 2010. Clinical data, as required by law, primarily consisted of a feasibility study conducted in 44 patients with gastro-esophageal reflux disease. However, a study comparing magnetic sphincter implantation versus fundoplication (the current standard of care) is lacking. Table 1 provides a selective overview of this and several other more recent medical devices that have already had an impact or could have a future impact on
general surgery. For most of these ‘innovations’, high-quality evidence is either lacking or shows no relevant improvement over current standards of surgery. Clinicians should therefore always keep in mind that new CE-marked medical devices are potentially ineffective. Especially for high-risk devices, this implies that the riskbenefit ratio is uncertain and may invert to more harm than benefit if future studies fail to show the anticipated benefits [2–4]. Recently, orthopedic surgeons had to learn this bitter lesson when metal-on-metal hip implants were found to fail in an alarmingly high proportion of patients [5]. Several other examples show that among the large number of medical devices with unknown effectiveness, some will turn out to be ineffective or even harmful. It can only become evident whether this is the case after higher-level clinical studies have been performed [4, 6, 7]. Such studies are often performed only when a device company plans to enter the US market. As the Food and Drug Administration (FDA) usually— but not always—requests better clinical evidence than European notified bodies, new high-risk devices are usually available about 2 years earlier on the market in Europe as compared to the United States [8–11]. During this time span (and even longer, if the device is not marketed in the United States), surgeons in Europe have to gamble with the risk of using or implanting ineffective or harmful devices [12]. Surgeons are used to making decisions under uncertainty and time pressure, but it can be extremely difficult to choose between innovation and patient safety. However, a tendency often prevails to be innovative and to suppress one’s doubts, even if the clinical need for a new device is limited [13, 14]. Surgeons may sometimes even face pressure from patients and the media to introduce innovations with perceived added value. In an area where competition between hospitals is intense, one might choose to use an innovation just because the local media will hail this event as a sign of a hospital’s quality. However, a more rational and structured assessment is necessary, and this should include a thorough review of the new device’s advantages and disadvantages, with all issues clearly separated into those with and those without supporting clinical evidence [15]. Ideally, surgeons are assisted by a multidisciplinary team (or a standing hospital committee) with expertise in evaluating medical procedures in an evidence-based way [16–18]. If surgical journals provided a regular section on new medical devices, readers might be more interested in evidence-based and independent reviews. Clinical, economic and strategic arguments have to be weighed against one another. If a decision is made in a hospital to use a new device or procedure for which clinical data are sparse, there should always be some form of concurrent quality control, ideally within more formal research as described below, followed by a re-evaluation.
Langenbecks Arch Surg Table 1 Important new medical devices with an impact on general surgery
a
Evidence levels: 1 = randomized controlled trials (RCTs) or systematic review of RCTs; 2 = higher-quality (e.g. prospective) controlled studies; 3 = lower quality (e.g. retrospective) controlled studies; 4 = cohort studies without a control group (i.e. case series); 5 = non-clinical data or expert opinion
Highest level of evidencea
Key clinical studies or reviews
Current best conclusion on effectiveness
Titanium clips for appendectomy Single-incision multi-port trocars for appendectomy for cholecystectomy for colorectal resection Negative pressure wound therapy for chronic or acute skin wounds for anastomotic leakage Magnetic sphincter augmentation for gastro-esophageal reflux disease
1
[36]
unclear
1 1 2
[37] [38, 39] [40]
no relevant difference no relevant difference unclear
1 2
[41, 42] [43]
unclear unclear
4
[44, 45]
unclear
for fecal incontinence Electrical lower esophageal sphincter stimulation Sacral nerve stimulation for fecal incontinence Duodenal-jejunal bypass sleeve Biologic meshes for incisional hernia Ultrasonic dissection devices Robotic assistance for fundoplication for bariatric surgery for gastrectomy
3 4
[46, 47] [48]
unclear unclear
1
[49]
unclear
1 4 1
[50] [51] [52]
unclear unclear minor advantages
1 1 3
[53] [54] [55]
no relevant difference unclear unclear
Selecting between existing devices Once a new device has entered the market, several very similar products will commonly follow. This leaves the surgeon with the choice of either buying the original leading product or a similar follow-up product. This decision should again be based on a thorough assessment of product safety, clinical effectiveness and costs. All too often, traditional costcontainment efforts directed at device purchase prices will prefer cheaper products, even though data on safety and effectiveness are mostly absent. Follow-up products can usually be offered at a lower price, because the manufacturers of such devices save on innovation costs and are not obliged to submit the same amount of data as was necessary for the first product. The first innovative product often has to prove safety and technical performance on the basis of clinical data, whereas follow-up products can be CE marked on the basis of their technical equivalence to the first product. Non-clinical data alone (combined with clinical data from the literature) may therefore be sufficient for the market access of a ‘me-too product’, which allows the manufacturer to offer his product at a much lower price. Furthermore, follow-up products are often only inadequately blocked by current patent law. Principally, European patents are valid for 20 years, but it is often possible to construct similar devices without infringing patent law. Furthermore, scientific theories and medical
procedures are unpatentable. ‘Me-too products’ are therefore an early and frequent problem, especially when the new device is less complex, such as an interspinous spacer. As a result, investment in clinical trials sometimes does not pay off for innovative device manufacturers. This difference in the patenting of drugs and devices allows the prices of many new devices to fall quickly after market entry but on the other hand impedes the conduct of clinical research. In effect, clinical data—and especially head-to-head comparisons—are frequently lacking. When trying to find data on a single device or a group of medical devices, surgeons will often have difficulties in finding information, because preclinical and clinical data on medical devices may exist but are kept on file by the manufacturer. Transparency—or more precisely, the lack of it—has been identified as a major problem in the evaluation of medical devices [11, 19]. Currently, there is no obligation for manufacturers or notifying bodies to publish clinical results data from CE dossiers. Any such publication might even help competitor manufacturers and is thus avoided. In addition, the European Databank of Medical Devices (EUDAMED), which could give surgeons an overview of all recently approved medical devices, together with the supporting clinical and non-clinical data, is not publicly accessible. Thus, it is impossible for clinicians and patients to make informed choices between different medical devices licensed for the
Langenbecks Arch Surg
same indication. When making decisions, surgeons can rely only on marketing materials and a few published clinical studies. This explains why even scientific surgeons make use of clinical experience, theoretical insights and personal communication. In the end, the lack of data transparency leads to an often unstructured, heterogeneous and erroneous innovation management in surgical departments all over Europe. There is some hope for an increase in transparency of clinical data on medical devices through the revised European regulation. On 22 October 2013, the European Parliament agreed that a ‘summary of the safety and performance report should be publicly available via EUDAMED’ [1], but this new transparency applies only to high-risk medical devices. In this regard, lessons can be learned from the regulatory procedures in the United States, where all relevant data are publicly accessible. On the FDA website, it is easy, for example, to find out which adjustable gastric banding systems have been approved and which clinical data were submitted for approval. European surgeons should make better use of this information source, also because of the higher standards of regulatory approval in the United States. It is worthwhile remembering that PIP silicone implants, robot surgery for total hip arthroplasty and many other harmful devices were never licensed for use in the United States [12]. There are even examples of US companies that first introduced their devices to the European market due to the lower regulatory hurdles. In this regard, European patients are being used as guinea pigs, often without being properly informed about the risks and benefits of new devices [20].
Evaluating devices in the hospital setting ‘No innovation without evaluation.’ This was one of the key statements of the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) surgical experts group [21–24]. It has also been recommended to perform prospective studies in the early phase of surgical innovation, where patient selection criteria and learning curve effects still have to be optimized [25]. In the second or main phase of evaluation, RCTs should be conducted. The pitfall to be avoided is acceptance of preliminary non-randomized data as proof of the new devices or procedure’s superiority [26]. It is beyond question that the RCT is the study design of choice for an unbiased assessment of treatments, and this pertains also to medical devices and surgical procedures [27, 28]. Thus, it is best to initiate an RCT when changing treatment in any relevant way. In surgery, however, it may be first necessary to overcome the learning curve. This may be worthwhile for proper planning of the RCT, for which useful patient selection criteria, suitable outcome measures and realistic effect size estimates are crucial.
Nevertheless, even in the context of a prospective study without a control group, full reporting of all results is necessary to ensure the validity of data on procedure feasibility. Besides scientific reporting of complete intention-to-treat results on a consecutive series of patients, it is also important to be compliant with reporting requirements for medical devices. Although safe innovation requires full reporting of potential problems, many surgeons do not file reports of complications to their national authority or the device manufacturer [29–31]. The apparent but deceptive absence of critical or negative reports strongly contributes to the enthusiasm that surrounds many new medical devices in their early phase. Figure 1 shows the course that some new devices and procedures take, once the initial enthusiasm wanes. The European Parliament has lately emphasized the importance of reporting complications that have occurred with the use of medical devices. In the future, manufacturers have to provide periodic safety update reports (PSURs) for all class III medical devices. Until today, PSURs were required only for drugs (i.e. pharmacovigilance). This regulatory step therefore shows that devices can be effectively assessed by similar methods as drugs. However, such reporting is not yet deemed necessary for class IIb products, which represent the majority of surgical implants. Furthermore, the PSURs will largely remain unpublished. Registries have recently drawn a lot of attention to the provision of ‘real-world’ data on medical devices. When data collection is carried out in a complete and valid way, registry studies may in fact offer valuable insights about the safety, application and quality of innovative health care. Device manufacturers are therefore sometimes requested to perform observational clinical studies for the Post-Market Surveillance (PMS) of new devices. Surgeons also try to set up registries to study new procedures or new devices, such as biologic mesh implants for hernia repair [32] or natural orifice transluminal endoscopic surgery [33]. Nevertheless, registry studies and
Fig. 1 The seven stages in the career of a medical innovation as described in the key article by John B. McKinlay [26]
Langenbecks Arch Surg
other observational studies do not generally allow reliable conclusions on effectiveness. It is often left to the scientific tenacity or enthusiasm of surgeons to fill these evidence gaps. The funding of clinical research, however, remains a constant challenge, and many highly relevant study ideas end up in low-quality research simply because most surgeons lack the resources to conduct their trials in multiprofessional collaboration.
Obtaining reimbursement for new devices As described above, many medical devices enter the European market without sufficient evidence of effectiveness. As the new European regulation will not essentially affect this highly problematic issue, it can be expected that different stakeholders will deal with this problem at a national level in each European country. It is easily understandable why national health insurance systems or statutory sickness funds deny payments for expensive medical devices with uncertain medical benefits. Highly innovative surgical departments will therefore experience problems with the reimbursement of new medical devices unless the manufacturer offers them a rebate. However, these reimbursement issues are highly dependent on the country a surgeon works in. They are thus considered to be beyond the scope of this article. A common trend in European health care is to link the reimbursement of new devices or procedures to participation in clinical research. This idea is often labelled as ‘coverage with evidence development’ (CED). Such a policy limits the application of new interventions to only a subset of wellselected patients treated within clinical trials in experienced centres. In addition, CED includes a reassessment of the intervention under question once the clinical trial has been completed. CED policies were initially installed in the United States and Canada, where they have proved to be useful [34, 35]. In late 2013, the new German government agreed on plans requiring that hospitals have to participate in clinical trials when using new high-risk medical devices in their patients. Hospitals that want to offer new surgical procedures will therefore have to train their staff in research methods, which in turn will also help to make better decisions on the use of existing devices. However, the key issue that will remain is: Who pays the costs of clinical research? It may also be difficult to draw a clear borderline between a new procedure and a new medical device.
Concluding remarks The vast majority of medical devices are safe and effective. This article is not intended to worry patients or surgeons, but the increasing complexity and invasiveness of medical
devices require a more critical attitude towards new products than previously shown. Scientific assessment of new medical devices should be as rigorous and regulated as for any other potentially harmful (or expensive) medical innovation. Surgeons should be reluctant to apply or implant new high-risk devices before high-quality evidence is published. In this context, it is a fundamental element of medical practice to appropriately inform the patient. As it is unlikely that the European regulation on device approval will become stricter, the reimbursement of medical devices will come increasingly into focus. Device manufacturers will become accustomed to the idea that RCTs are indispensable in determining clinical risks and benefits. The reimbursement of new high-risk devices will be formally linked to positive RCT results. Scientific surgeons who participate and collaborate in the different research activities will gain influence, as they will be the first to use and evaluate new devices for the benefit of patients.
Acknowledgments The authors thank Natalie McGauran for editorial support. Conflicts of interest None
References 1. European Parliament (2013) Amendments adopted by the European Parliament on 22 October 2013 on the proposal for a regulation of the European Parliament and of the Council on medical devices, and amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009. http://www.europarl.europa.eu/ sides/getDoc.do?type=TA&language=EN&reference=P7-TA-2013428 02 Accessed.January.2014 2. Hulstaert F, Neyt M, Vinck I, Stordeur S, Huic M, Sauerland S, Kuijpers MR, Abrishami P, Vondeling H, Van Brabandt H (2011) The pre-market clinical evaluation of innovative high-risk medical devices (KCE report 158C). Belgian Health Care Knowledge Centre, Brussels (Belgium) 3. Herrmann-Frank A, Lelgemann M (2013) Neue Medizinprodukte: Unzureichende Datenlage [New medical devices: insufficient evidence]. Dt Ärztebl 110(10):A432–A434 4. German National Associations of Statutory Health Insurance Funds (2013) Medical devices: the myths and the truth. http://www.aok-bv. de/imperia/md/aokbv/politik/versicherte/thesenpapier_gross_0913_ engl_1.pdf.02 Accessed January 2014 5. Cohen D (2011) Out of joint: the story of the ASR. BMJ 342:d2905 6. Cohen D (2012) EU approval system leaves door open for dangerous devices. BMJ 345:e7173 7. Storz-Pfennig P, Schmedders M, Dettloff M (2013) Trials are needed before new devices are used in routine practice in Europe. BMJ 346: f1646 8. Kramer DB, Xu S, Kesselheim AS (2012) Regulation of medical devices in the United States and European Union. N Engl J Med 366(9):848–855 9. Curfman GD, Redberg RF (2011) Medical devices—balancing regulation and innovation. N Engl J Med 365(11):975–977
Langenbecks Arch Surg 10. Kramer DB, Xu S, Kesselheim AS (2012) How does medical device regulation perform in the United States and the European Union? A systematic review. PLoS Med 9(7):e1001276 11. Krüger LJ, Wild C (2013) Evidence requirements for the authorization and reimbursement of high-risk medical devices in the USA, Europe, Australia and Canada (HTA Project Report No. 73). Ludwig Boltzmann Institute Health Technology Assessment, Vienna 12. Food and Drug Administration (FDA) (2012) Unsafe and ineffective devices approved in the EU that were not approved in the US. http:// www.elsevierbi.com/∼/media/Supporting%20Documents/The% 20Gray%20Sheet/38/20/FDA_EU_Devices_Report.pdf 02 Accessed January 2014 13. Anand R, Graves SE, de Steiger RN, Davidson DC, Ryan P, Miller LN, Cashman K (2011) What is the benefit of introducing new hip and knee prostheses? J Bone Joint Surg Am 93(Suppl 3):51–54 14. Lieberman JR, Wenger N (2004) New technology and the orthopaedic surgeon: are you protecting your patients? Clin Orthop Relat Res 429:338–341 15. Neugebauer EA, Becker M, Buess GF, Cuschieri A, Dauben HP, Fingerhut A, Fuchs KH, Habermalz B, Lantsberg L, Morino M, Reiter-Theil S, Soskuty G, Wayand W, Welsch T (2010) EAES recommendations on methodology of innovation management in endoscopic surgery. Surg Endosc 24(7):1594–1615 16. Selbmann HK (1997) Qualitäts—und Innovationsmanagement in der Chirurgie im Dienste des Patienten [Quality and innovation management in surgery for the patient’s benefit]. Langenbecks Arch Chir Suppl Kongressbd 114:872–879 17. Wright JG, Weinstein S (2013) The innovation cycle: a framework for taking surgical innovation into clinical practice. J Bone Joint Surg Am 95(21):e1641–e1645 18. Poulin P, Austen L, Kortbeek JB, Lafreniere R (2012) New technologies and surgical innovation: five years of a local health technology assessment program in a surgical department. Surg Innov 19(2):187–199 19. Hulstaert F, Neyt M, Vinck I, Stordeur S, Huic M, Sauerland S, Kuijpers MR, Abrishami P, Vondeling H, Flamion B, Garattini S, Pavlovic M, van Brabandt H (2012) Pre-market clinical evaluations of innovative high-risk medical devices in Europe. Int J Technol Assess Health Care 28(3):278–284 20. Falagas ME, Korbila IP, Giannopoulou KP, Kondilis BK, Peppas G (2009) Informed consent: how much and what do patients understand? Am J Surg 198(3):420–435 21. McCulloch P, Cook JA, Altman DG, Heneghan C, Diener MK (2013) IDEAL framework for surgical innovation 1: the idea and development stages. BMJ 346:f3012 22. Ergina PL, Barkun JS, McCulloch P, Cook JA, Altman DG (2013) IDEAL framework for surgical innovation 2: observational studies in the exploration and assessment stages. BMJ 346:f3011 23. Cook JA, McCulloch P, Blazeby JM, Beard DJ, Marinac-Dabic D, Sedrakyan A (2013) IDEAL framework for surgical innovation 3: randomised controlled trials in the assessment stage and evaluations in the long term study stage. BMJ 346:f2820 24. McCulloch P, Altman DG, Campbell WB, Flum DR, Glasziou P, Marshall JC, Nicholl J, Aronson JK, Barkun JS, Blazeby JM, Boutron IC, Clavien PA, Cook JA, Ergina PL, Feldman LS, Maddern GJ, Reeves BC, Seiler CM, Strasberg SM, Meakins JL, Ashby D, Black N, Bunker J, Burton M, Campbell M, Chalkidou K, Chalmers I, de Leval M, Deeks J, Grant A, Gray M, Greenhalgh R, Jenicek M, Kehoe S, Lilford R, Littlejohns P, Loke Y, Madhock R, McPherson K, Meakins J, Rothwell P, Summerskill B, Taggart D, Tekkis P, Thompson M, Treasure T, Trohler U, Vandenbroucke J (2009) No surgical innovation without evaluation: the IDEAL recommendations. Lancet 374(9695):1105–1112 25. Ramsay CR, Grant AM, Wallace SA, Garthwaite PH, Monk AF, Russell IT (2000) Assessment of the learning curve in health technologies. A systematic review. Int J Technol Assess Health Care 16(4):1095–1108
26. McKinlay JB (1981) From “promising report” to “standard procedure”: seven stages in the career of a medical innovation. Milbank Mem Fund 59:374–411 27. Walters BC, Sackett DL (1991) Why clinical research? In: Troidl H, Spitzer WO, McPeek B et al (eds) Principle and practice of research: strategies for surgical investigators, 2nd edn. Springer, New York, pp 231–248 28. Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (2011) Allgemeine Methoden: Version 4.0. https://www.iqwig.de/download/ IQWiG_Methoden_Version_4_0.pdf.02 Accessed January 2014 29. Samore MH, Evans RS, Lassen A, Gould P, Lloyd J, Gardner RM, Abouzelof R, Taylor C, Woodbury DA, Willy M, Bright RA (2004) Surveillance of medical device-related hazards and adverse events in hospitalized patients. JAMA 291(3):325–334 30. Cooper MA, Ibrahim A, Lyu H, Makary MA (2013) Underreporting of robotic surgery complications. J Healthc Qual 31. Fuller J, Ashar BS, Carey-Corrado J (2005) Trocar-associated injuries and fatalities: an analysis of 1399 reports to the FDA. J Minim Invasive Gynecol 12(4):302–307 32. Ansaloni L, Catena F, Coccolini F, Negro P, Campanelli G, Miserez M (2009) New “biological” meshes: the need for a register. The EHS registry for biological prostheses: call for participating European surgeons. Hernia 13(1):103–108 33. Arezzo A, Zornig C, Mofid H, Fuchs KH, Breithaupt W, Noguera J, Kaehler G, Magdeburg R, Perretta S, Dallemagne B, Marescaux J, Copaescu C, Graur F, Szasz A, Forgione A, Pugliese R, Buess G, Bhattacharjee HK, Navarra G, Godina M, Shishin K, Morino M (2013) The EURO-NOTES clinical registry for natural orifice transluminal endoscopic surgery: a 2-year activity report. Surg Endosc 27(9):3073–3084 34. Tunis SR, Pearson SD (2006) Coverage options for promising technologies: Medicare’s ‘coverage with evidence development’. Health Aff (Millwood) 25(5):1218–1230 35. Daniel GW, Rubens EK, McClellan M (2013) Coverage with evidence development for medicare beneficiaries: challenges and next steps. JAMA Intern Med 173(14):1281–1282 36. Ates M, Dirican A, Ince V, Ara C, Isik B, Yilmaz S (2012) Comparison of intracorporeal knot-tying suture (polyglactin) and titanium endoclips in laparoscopic appendiceal stump closure: a prospective randomized study. Surg Laparosc Endosc Percutan Tech 22(3):226–231 37. Markar SR, Karthikesalingam A, Di Franco F, Harris AM (2013) Systematic review and meta-analysis of single-incision versus conventional multiport appendicectomy. Br J Surg 100(13):1709–1718 38. Geng L, Sun C, Bai J (2013) Single incision versus conventional laparoscopic cholecystectomy outcomes: a meta-analysis of randomized controlled trials. PLoS One 8(10):e76530 39. Saad S, Strassel V, Sauerland S (2013) Randomized clinical trial of single-port, minilaparoscopic and conventional laparoscopic cholecystectomy. Br J Surg 100(3):339–349 40. Maggiori L, Gaujoux S, Tribillon E, Bretagnol F, Panis Y (2012) Single-incision laparoscopy for colorectal resection: a systematic review and meta-analysis of more than a thousand procedures. Colorectal Dis 14(10):e643–e654 41. Gregor S, Maegele M, Sauerland S, Krahn J, Peinemann F, Lange S (2008) Negative pressure wound therapy: a vacuum of evidence? Arch Surg 143(2):189–196 42. Webster J, Scuffham P, Sherriff KL, Stankiewicz M, Chaboyer WP (2012) Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention. Cochrane Database Syst Rev 4: Cd009261 43. Mees ST, Palmes D, Mennigen R, Senninger N, Haier J, Bruewer M (2008) Endo-vacuum assisted closure treatment for rectal anastomotic insufficiency. Dis Colon Rectum 51(4):404–410 44. Bonavina L, Saino G, Bona D, Sironi A, Lazzari V (2013) One hundred consecutive patients treated with magnetic sphincter
Langenbecks Arch Surg
45.
46.
47.
48.
49.
augmentation for gastroesophageal reflux disease: 6 years of clinical experience from a single center. J Am Coll Surg 217(4):577–585 Ganz RA, Peters JH, Horgan S, Bemelman WA, Dunst CM, Edmundowicz SA, Lipham JC, Luketich JD, Melvin WS, Oelschlager BK, Schlack-Haerer SC, Smith CD, Smith CC, Dunn D, Taiganides PA (2013) Esophageal sphincter device for gastroesophageal reflux disease. N Engl J Med 368(8):719–727 Wong MT, Meurette G, Stangherlin P, Lehur PA (2011) The magnetic anal sphincter versus the artificial bowel sphincter: a comparison of 2 treatments for fecal incontinence. Dis Colon Rectum 54(7):773–779 Wong MT, Meurette G, Wyart V, Lehur PA (2012) Does the magnetic anal sphincter device compare favourably with sacral nerve stimulation in the management of faecal incontinence? Colorectal Dis 14(6): e323–e329 Rodriguez L, Rodriguez P, Gomez B, Ayala JC, Saba J, PerezCastilla A, Galvao Neto M, Crowell MD (2013) Electrical stimulation therapy of the lower esophageal sphincter is successful in treating GERD: final results of open-label prospective trial. Surg Endosc 27(4):1083–1092 Thin NN, Horrocks EJ, Hotouras A, Palit S, Thaha MA, Chan CL, Matzel KE, Knowles CH (2013) Systematic review of the clinical effectiveness of neuromodulation in the treatment of faecal incontinence. Br J Surg 100(11):1430–1447
50. Zechmeister-Koss I, Huic M, Fischer S (2013) Duodenal-jejunal bypass sleeve for the treatment of obesity with or without type II diabetes mellitus (EUnetHTA final report). http://www.eunethta.eu/ sites/5026.fedimbo.belgium.be/files/Endobarrier_Assessment.pdf.02 Accessed January 2014 51. Slater NJ, van der Kolk M, Hendriks T, van Goor H, Bleichrodt RP (2013) Biologic grafts for ventral hernia repair: a systematic review. Am J Surg 205(2):220–230 52. Contin P, Goossen K, Grummich K, Jensen K, Schmitz-Winnenthal H, Büchler MW, Diener MK (2013) ENERgized vessel sealing systems versus CONventional hemostasis techniques in thyroid surgery—the ENERCON systematic review and network meta-analysis. Langenbecks Arch Surg 398(8):1039–1056 53. Wang Z, Zheng Q, Jin Z (2012) Meta-analysis of robot-assisted versus conventional laparoscopic Nissen fundoplication for gastrooesophageal reflux disease. ANZ J Surg 82(3):112–117 54. Cirocchi R, Boselli C, Santoro A, Guarino S, Covarelli P, Renzi C, Listorti C, Trastulli S, Desiderio J, Coratti A, Noya G, Redler A, Parisi A (2013) Current status of robotic bariatric surgery: a systematic review. BMC Surg 13(1):53 55. Marano A, Choi YY, Hyung WJ, Kim YM, Kim J, Noh SH (2013) Robotic versus laparoscopic versus open gastrectomy: a metaanalysis. J Gastric Cancer 13(3):136–148
